This is not in favour of the implication of the MOG gene in the genetic component of multiple sclerosis, unless different independent mutations have occurred within this gene.
The primary target autoantigen in MS has yet to be definitively identified, but as well as the major myelin proteins, it is now clear that minor myelin components, such as myelin oligodendrocyte glycoprotein (MOG) may play a primary role in disease initiation.
The present study was designed to analyze whether differences in genes that encode myelin proteins influence susceptibility to MS. We performed linkage analysis of MS to markers in chromosomal regions that include the genes encoding myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMGP), and myelin oligodendrocyte glycoprotein (MOG) in a well-characterized population of 65 multiplex MS families consisting of 399 total individuals, 169 affected with MS and 102 affected sibpairs.
The myelin oligodendrocyte glycoprotein (MOG): a model for antibody-mediated demyelination in experimental autoimmune encephalomyelitis and multiple sclerosis.
Analysis of the first 100 MS patients for six IL4R variants showed an increased frequency of the R551 variant in MS patients versus healthy controls and carriage of the same IL4R variant was weakly associated with myelin oligodendrocyte glycoprotein (MOG) autoantibody production.
This present article will discuss recently published and some preliminary data on the immunopathogenic role of antibodies against myelin oligodendrocyte glycoprotein (MOG) and other myelin/nonmyelin targets in multiple sclerosis, as well as possible clinical implications for prognosis and therapy in the future.
This article reviews experimental data currently available on specificity and pathogenic roles of T cell and antibody responses against MOG, which have implications relevant to multiple sclerosis and related disorders.
Interestingly, the same peptide was presented by human B cells expressing HLA-DR4 (DRB1*0401), suggesting a role for the identified MOG epitopes in the pathogenesis of human MS.
The binding of MOG 146-154 was comparable or better than myelin basic protein 85-99, which is the dominant myelin basic protein epitope in context with HLA-DRB1*1501 molecules in MS patients.
We have addressed this question for the putative multiple sclerosis(MS) autoantigens alphaB-crystallin, S100beta, proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG)-alpha and MOG-beta isoforms, using quantitative RT-PCR on human thymus (total, cell fractions and microdissected specimen) and on a panel of peripheral tissues. alphaB-crystallin, S100beta and the DM20 isoform of PLP were clearly expressed in the thymus and also in selected peripheral tissues.
T cell autoreactivity to MOG was directed against peptides 1-20, 31-50, 61-80 and 91-110, of which three are also immunodominant epitopes for MOG in MS. A strong B cell response to MOG was observed in all transgenic mice, and major B cell epitopes recognized were located within amino acids 1-30, 51-80 and 101-120 of human MOG, which consists of two epitopes reported in MS. Transgenic mice used in this study recognized the immunodominant MOG epitopes similar to HLA class II-restricted human T cells, and would therefore be valuable in elucidating the roles of HLA class II genes and autoantigens in MS.
Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) induced in DA (RT1(av1)) rats resembles multiple sclerosis (MS) in many aspects since central nervous system (CNS) pathology shows inflammation, demyelination and axonal loss.
Myelin oligodendrocyte glycoprotein (MOG) is a minor component of central nervous system myelin presumably implicated in the pathogenesis of Multiple Sclerosis (MS).
The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive Ab in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS.
Anti-MOG antibodies are not specific for MS; however, they may characterize a subset of MS patients and this may be revealed by serial assays in relation to changing disease phase.
The enhancing effect of the mutated Ncf1 could also be shown to be more general in that it enhanced myelin oligodendrocyte glycoprotein protein-induced experimental autoimmune encephalomyelitis, a model for multiple sclerosis.
This fact, combined with a sequence relationship between BTNL2 and myelin oligodendrocyte glycoprotein, an autoantigen associated with MS, makes the gene an attractive candidate.
Astrocytes have been shown to present myelin basic protein (MBP) and proteolipid protein (PLP) to T cells, but it has remained unresolved whether astrocytes present myelin oligodendrocyte glycoprotein (MOG), which has been implicated as an important autoantigen in MS.
IgG but not IgM antibody titers to native MOG were significantly higher in MS patients compared with different control groups with the highest prevalence in primary progressive MS patients.